title: Importance of hedgehog interacting protein and other lung function genes in asthma.
abstract: BACKGROUND
  Two recent large meta-analyses of genome-wide association studies of lung function in general populations of European descent identified 11 candidate genes/regions. The importance of these genes in lung function in white and African American subjects with asthma is unknown.
  
  
  OBJECTIVE
  To determine whether genes that regulate lung function in general populations are associated with lung function abnormalities in subjects with asthma from different racial groups.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) were tested in 5 asthma populations (N = 1441) for association with pulmonary function, and meta-analysis was performed across populations. The SNPs with the highest significance were then tested for association with bronchodilator reversibility and bronchial hyperresponsiveness to methacholine. A joint analysis of consistently replicated SNPs was performed to predict lung function in asthma.
  
  
  RESULTS
  Hedgehog interacting protein (HHIP) on chromosome 4q31 was associated with lung function in all 5 populations (rs1512288: P(meta) = 9.62E-05 and 3.23E-05 for percent predicted FEV(1) [ppFEV(1)] and percent predicted forced vital capacity [ppFVC], respectively). The SNPs in HHIP were also associated with reversibility (P < .05) but not bronchial hyperresponsiveness to methacholine. Because of differences in linkage disequilibrium in the African American subjects, the most relevant SNPs in HHIP were identified. A subset of normal lung function genes, including HHIP, family with sequence similarity 13, member A (FAM13A), and patched homolog 1 (PTCH1), together predict lung function abnormalities, a measure of severity in white and African American subjects with asthma.
  
  
  CONCLUSIONS
  A subset of the genes, including HHIP, that regulate lung function in general populations are associated with abnormal lung function in asthma in non-Hispanic white and African American subjects.
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Xingnan
authors.initials: X
authors.lastname: Li
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ampleford
authors.forename: Huashi
authors.initials: H
authors.lastname: Li
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
mesh_terms: D001741:Black or African American / Q000235:genetics; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008562:Membrane Glycoproteins / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D012129:Respiratory Function Tests; D019699:Thrombospondins / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C117596:HHIP protein, human; D008562:Membrane Glycoproteins; C106075:NOTCH4 protein, human; C514653:PID1 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D019699:Thrombospondins